Phytochemicals in Anticancer Drug Development.

Background: In spite of major technological advances in conventional therapies, cancer continues to remain the leading cause of mortality worldwide. Phytochemicals are gradually emerging as a rich source of effective but safer agents against many life-threatening diseases.

Methods: Various phytochemicals with reported anticancer activity have been simply categorized into major phytoconstituents- alkaloids, polyphenols, saponins, tannins and terpenoids.

Color additives: legislative perspective in the United States, Europe, Australia, and India.

In most countries, their regulatory bodies which control food, drugs, and cosmetics are responsible for regulating all the color additives to ensure that they are safe with those products, ensuring that they contain only approved ingredients, and that they are accurately labeled. Permitted colors are subject to rigorous safety standards prior to their approval and prior to the release of their specific use. Although a colorant may have approval in several countries, its use, level of use, specifications, acceptance criteria, and labeling requirements may differ from one country to another.

Selection of color additives: a regulatory view.

Color additives have a unique place in the categories of the excipients. However, most of the color additives are complex heterogeneous organic compounds. In pharmaceuticals, colors are used in various oral (solid, liquid) and topical dosage form.

Diverse models for the prediction of HIV integrase inhibitory activity of substituted quinolone carboxylic acids.

In the present study both classification and correlation techniques of diverse nature were successfully employed for the development of models for the prediction of human immunodeficiency virus (HIV) integrase inhibitory activity using a dataset comprising 50 analogs of quinolone carboxylic acid. The values of various molecular descriptors (MDs) for each analog in the dataset were computed using the MDS V-life science QSAR plus module. The values of other MDs which are not part of MDS V-life science were computed using an in-house computer program.

Superaugmented eccentric distance sum connectivity indices: novel highly discriminating topological descriptors for QSAR/QSPR.

Four highly discriminating fourth-generation topological indices (TIs), termed as superaugmented eccentric distance sum connectivity indices, as well as their topochemical versions (denoted by , , and ), have been conceptualized in this study. The values of these indices for all possible structures with three, four, and five vertices containing one heteroatom were computed using an in-house computer program. The proposed superaugmented eccentric distance sum connectivity topochemical indices exhibited exceptionally high discriminating power, low degeneracy, and high sensitivity toward both the presence and the relative position of heteroatom(s) for all possible structures with five vertices containing at least one heteroatom.

Models for the prediction of receptor tyrosine kinase inhibitory activity of substituted 3-aminoindazole analogues.

The inhibition of tumor angiogenesis has become a compelling approach in the development of anticancer drugs. In the present study, topological models were developed through decision tree and moving average analysis using a data set comprising 42 analogues of 3-aminoindazoles. A total of 22 descriptors (distance based, adjacency based, pendenticity and distance-cum-adjacency based) were used.

Models for antitubercular activity of 5â-O-[(N-Acyl)sulfamoyl]adenosines.

The relationship between topological indices and antitubercular activity of 5â-O-[(N-Acyl)sulfamoyl]adenosines has been investigated. A data set consisting of 31 analogues of 5â-O-[(N-Acyl)sulfamoyl]adenosines was selected for the present study. The values of numerous topostructural and topochemical indices for each of 31 differently substituted analogues of the data set were computed using an in-house computer program.

Development of modified dosage form for enhancement of dissolution rate through amalgamation of solid dispersion and cube sugar or sintering technology using famotidine as a model drug.

An amalgamation of solid dispersion and cube sugar or sintering technologies was utilized for preparing a high dissolution rate, fast-release dosage form for poorly water soluble drug(s). Famotidine was employed as a model drug. Solid dispersion particles of famotidine were prepared using the fusion method employing xylitol as an hydrophilic carrier, and the particles' solid state performance was characterized by means of differential scanning calorimetry, Fourier transformed infrared spectroscopy, and X-ray powder diffractometry.

Predicting anti-HIV activity of dimethylaminopyridin-2-ones: computational approach using topochemical descriptors.

In this study, relationship between the topochemical indices and anti-HIV activity of dimethylaminopyridin-2-ones has been investigated. Three topochemical indices of diverse nature, i.e.

Validation of topochemical models for the prediction of permeability through the blood-brain barrier.

Recently published topochemical models for permeability through the blood-brain barrier were validated and cross-validated in the present study. Five models based on three topochemical indices, Wiener's topochemical index - a distance-based topochemical descriptor, molecular connectivity topochemical index - an adjacency-based topochemical descriptor and eccentric connectivity topochemical index - an adjacency-cum-distance based topochemical descriptor, for permeability of structurally and chemically diverse molecules through blood-brain barrier were used in the present investigation. A data set comprising 62 structurally and chemically diverse compounds was selected.

Topochemical models for prediction of telomerase inhibitory activity of flavonoids.

In the present study, the relationship between the topochemical indices and telomerase inhibitory activity of flavonoids has been investigated. Three topochemical indices, Wiener's topochemical index (a distance-based topochemical descriptor), molecular connectivity topochemical index (an adjacency-based topochemical descriptor) and superadjacency topochemical index (an adjacency cum distance-based topochemical descriptor) were used for the present investigation. The values of the Wiener's topochemical index, molecular connectivity topochemical index and superadjacency topochemical index for each of the 30 analogues comprising the data set were computed using an in-house computer program.

Topochemical models for the prediction of voltage-gated sodium channel binding activity of hydantoins and related non-hydantoins.

The relationship of Wiener's topochemical index-a distance based topochemical index, molecular connectivity topochemical index-an adjacency based topochemical index and eccentric connectivity topochemical index-an adjacency-cum-distance based topochemical index with sodium channel binding activity has been investigated. A dataset comprising 50 hydantoins and related non-hydantoins was selected. The dataset was divided equally into training and test sets.

Prediction of h5-HT2A receptor antagonistic activity of arylindoles: computational approach using topochemical descriptors.

Relationship between the topochemical indices and h5-HT2A receptor antagonistic activity of arylindoles has been investigated. Three topochemical indices, Wiener's topochemical index--a distance-based topochemical descriptor, molecular connectivity topochemical index--an adjacency-based topochemical descriptor and eccentric connectivity topochemical index--an adjacency-cum-distance based topochemical descriptor, were used for the present investigation. A data set comprising 31 differently substituted arylindoles was selected for the present study.

Topological model for the prediction of MRP1 inhibitory activity of pyrrolopyrimidines and templates derived from pyrrolopyrimidine.

Relationship between Wiener's index--a distance-based topological descriptor and multidrug-resistance-associated protein (MRP1) inhibitory activity of pyrrolopyrimidines and their derivatives has been investigated. A dataset comprising of 82 analogues of pyrrolopyrimidine was selected for the present study. The values of Wiener's index were computed for each of the 82 analogues using an in-house computer program.

Topochemical models for prediction of cyclin-dependent kinase 2 inhibitory activity of indole-2-ones.

The relationship between the topochemical indices and cyclin-dependent kinase 2 (CDK2) inhibitory activity of indole-2-ones has been investigated. The relationship of topochemical versions of well known topological indices of Wiener's index--a distance-based topological descriptor, molecular connectivity index, an adjacency-based topological descriptor and eccentric connectivity index--an adjacency-cum-distance based topological descriptor with CDK2 inhibitory activity of indole-2-ones has been investigated. A data set comprising 67 analogues of substituted indole-2-ones was selected for the present investigation.

Topochemical models for prediction of anti-tumor activity of 3-aminopyrazoles.

Relationship between topochemical indices and inhibition of CDK2/cyclin A by 3-aminopyrazoles was investigated using a data set comprising of 42 3-aminopyrazoles. Three topochemical indices--the Wiener's topochemical index--a distance based topochemical index, atomic molecular connectivity index--an adjacency based topochemical index and superadjacency topochemical index--an adjacency-cum-distance based topochemical index were used for the present investigations. The values of Wiener's topochemical index, atomic molecular connectivity index and superadjacency topochemical index for each of the 42 compounds comprising the data set were computed using an in-house computer program.

Topological models for the prediction of HIV-protease inhibitory activity of tetrahydropyrimidin-2-ones.

Relationship between the topological indices and HIV-protease inhibitory activity of tetrahydropyrimidine-2-ones has been investigated. Three topological indices, Wiener's index--a distance based topological descriptor, Zagreb group parameter--an adjacency based topological descriptor and eccentric connectivity index--an adjacency-cum-distance based topological descriptor were used for the present investigations. A dataset comprising of 80 substituted tetrahydropyrimidine-2-one analogues was selected for the present studies.

Predicting anti-HIV activity of 2,3-diaryl-1,3-thiazolidin-4-ones: computational approach using reformed eccentric connectivity index.

The eccentric connectivity index, which has recently been employed successfully for the development of numerous mathematical models for the prediction of biological activities of diverse nature, has been reformed to overcome its limitations caused by degeneracy and insensitivity towards heteroatoms. The reformed eccentric connectivity index, termed the eccentric connectivity topochemical index, overcomes the limitations of the eccentric connectivity index by exhibiting very low degeneracy and displaying sensitivity to both the presence and relative position of heteroatoms without compromizing the discriminating power of the eccentric connectivity index. The relationship of the eccentric connectivity topochemical index, eccentric connectivity index and Wiener's index with regard to the anti-HIV activity of 2, 3-diaryl-1, 3-thiazolidin-4-one derivatives was subsequently investigated.

Predicting anti-HIV activity of TIBO derivatives: a computational approach using a novel topological descriptor.

A novel highly discriminating adjacency-cum-distance-based topological descriptor, termed the adjacent eccentric distance sum index, has been conceptualized and its discriminating power investigated with regard to the anti-HIV activity of 4,5,6,7-tetrahydro-imidazo-[4,5,1- jk] [1,4] benzodiazepin-2 (1 H)-one (TIBO) derivatives. The discriminating power of the adjacent eccentric distance sum index was compared with that of the eccentric connectivity index - another adjacency-cum-distance-based topological descriptor. The values of the eccentric connectivity index and the adjacent eccentric distance sum index of each of 121 analogues comprising the data set were computed and active ranges were identified.